The present invention generally relates to apparatuses for the delivery of biological composites that facilitate imbibation and infiltration of porous substrates with biological materials to form biological composites, together with systems and kits comprising the same. This application also relates to methods for the preparation and delivery of biologically active composites that may comprise both a substrate material and biological materials. The biological composites preferably comprise an inorganic substrate, such as for example, a calcium phosphate inorganic material like beta-tricalcium phosphate (xe2x80x9cxcex2-TCPxe2x80x9d), and a biological component, such as for example, bone marrow aspirate (xe2x80x9cBMAxe2x80x9d).
When bone integrity is threatened by trauma, infection, congenital malformation, tumor growth, or degenerative diseases, bone grafting can be used to encourage the affected bone to regenerate and heal. The graft functions in a manner similar to cancellous bone, supporting new tissue growth by providing the bone and blood cells with a matrix through which to interweave as they reconnect the bone fragments. For a bone graft to be successful, three processes that mimic natural events in cancellous bone should take place: osteoinduction, osteogenesis, and osteoconduction. Osteoinduction is the biologically mediated recruitment and differentiation of cell types essential for bone. Osteogenesis is the process of bone formation through cellular osteoblastic activity, which, in turn, is dependent upon the presence of osteoprogenitor stem cells. Lastly, osteoconduction is the apposition of growing bone to the three-dimensional surface of a suitable scaffold provided by the graft.
Orthopedists are currently using a variety of materials that enhance, to various degrees, these three processes. The basic types of bone substitutes, which are sometimes used alone and sometimes in combination, comprise the autograft, cadaveric allograft, xenograft, and several types of graft materials.
Ideally, materials used for bone grafts will provide for osteogenesis, osteoinduction, and osteoconduction, resulting in vigorous new bone growth that will repair the defect. One effective bone graft material in current use is the autogenous cancellous bone graft. However, survival of intrinsic osteogenic stem cells in the autograft is not optimal, and the harvesting process (generally from the iliac crest) results in considerable morbidity to the patient. As a result, alternative bone-grafting strategies have been investigated. The development of composite grafts that combine synthetic cancellous bone void fillers with autogenous bone-forming cells could simplify and improve grafting procedures.
There have been devices in the art which allow for the mixing of bodily fluids within a syringe comprising inorganic particles and morsels. Few of these devices, however, provide a device that allows for the formation of a biologically active composite capable of fostering osteoinduction, osteogenesis, and osteoconduction.
For example, U.S. Pat. No. 4,551,135 (xe2x80x9cGormanxe2x80x9d) discloses a syringe for the extrusion of a semi-plastic mass, having a barrel which may be pre-loaded with a semi-plastic mass or one component of a multi-component plasticizable mixture, and which may be fitted at its exit end with removable means for making an inter-connection with a filling syringe to a add a second liquid, component to the dispensing syringe. In a preferred embodiment, Gorman teaches that the barrel is flared toward its lower end.
U.S. Pat. No. 4,065,360 (xe2x80x9cKrebxe2x80x9d) discloses a syringe device for drawing blood or other fluids directly into a sealed sterile environment. The syringe includes a hollow housing, a movable piston, at least one culture cavity in the walls of the housing and sealing means about the periphery of the movable piston such that after fluid is withdrawn into contact with the culture cavities, the piston may be moved back upwardly to seal the culturing media with respect to the outside environment and to the chamber within the syringe to allow for sterile culturing of the fluid. Kreb also teaches a hollow nipple means attached to one end of the syringe adapted to receive a needle.
U.S. Pat. No. 4,801,263 (xe2x80x9cClarkxe2x80x9d) discloses a device for placing osseous implant substances into interdental alveolar bone defects. The device includes a syringe barrel member having an inlet and an outlet, a syringe plunger member having a piston rod, grasping members attached to an external surface of the syringe barrel and a threaded nozzle coupler attached to the exterior of the barrel member for allowing an extended nozzle member, preferably curved, to be attached to the syringe barrel.
U.S. Pat. No. 5,772,665 (xe2x80x9cGladxe2x80x9d) discloses a device for mixing a pharmaceutical composition which includes a hollow body having an outlet sealed by a removable closure, a plunger slidable therein in sealing contact with the inner wall of the hollow body, actuating means for displacing the plunger, a chamber for housing the pharmaceutical composition, a filling conduit connected to the chamber, and a check valve associated with the conduit and the chamber which prevents flow from the chamber but permits flow into the chamber through the conduit. Glad discloses that water can be added to the chamber in one of two ways: withdrawing the plunger upward and allowing water to enter through the lower end; or by placing the lid on the lower end, removing the plunger and pouring/injecting water into the upper opening. When the filling is complete, either the lid is applied to the lower end or the plunger is re-inserted into the hollow body, respectively.
U.S. Pat. Nos. 5,824,084 and 6,049,026 (referred to herein collectively as xe2x80x9cMuschlerxe2x80x9d) disclose a method of preparing a composite bone graft and apparatus for preparing an implantable graft, respectively, which includes a porous, biocompatible, implantable substrate, a container for retaining the substrate and for permitting flow of a bone marrow aspirate suspension (bone marrow aspirate that may include an isotonic solution and an anti-coagulant) completely through the substrate into an effluent container for receiving effluent of the bone marrow aspirate suspension from the container. Muschler also teaches a graft having an enriched population of connective tissue progenitor cells, the graft being the resultant product of the disclosed method and apparatus.
There is a need to provide for the formation and delivery of a highly porous, inorganic substrate that is rendered biologically active by the aspiration of a biological material into the device. Further, there is a need in the art to provide a method for restoring an osseous void that may be employed in situations that require the use of a bone void filler for filling voids or gaps that are not intrinsic to the stability of the bony structure. Moreover, there is a need in the art to provide a kit that can form a biologically active composite and deliver the composite mass into an osseous void thereby restoring the void.
The present invention provides an apparatus capable of housing a substrate material. The material is infiltrated with a biological substance to provide a biological composite. In one embodiment, the present invention provides an apparatus for preparing a biological composite comprising a material chamber, having a proximal end and a distal end, containing a calcium phosphate material having macro-, meso- and micro-porosity, the proximal end being sealingly closed by a movable plunger; and the distal end of the chamber being closed by a dismountable end cap, the end cap being provided with a point for attachment of an aspiration needle. In certain embodiments, the apparatus further comprises a closed end cap that is interchangeable with the dismountable end cap for sealing the material chamber between the plunger and the closed end cap.
In another embodiment of the present invention, there is provided a method for preparing a biological composite comprising the steps of: providing an apparatus comprising a material chamber comprising an inorganic, biologically compatible material having macro-, meso- and micro-porosity and having a proximal end and a distal end, the proximal end being sealingly closed by a movable plunger; the distal end of the chamber being closed by a dismountable end cap, the end cap being provided with a point for attachment of an aspiration needle; attaching the aspiration needle to the dismountable end cap; placing the aspiration needle into a situs of bone marrow; operating the plunger to draw a partial vacuum in the material chamber and to cause aspiration of bone marrow into the material chamber in an amount sufficient to substantially wet the biologically compatible morselate material; and maintaining the aspirate in contact with the biologically compatible composite under conditions effective to cause at least partial coalescence of the marrow-morselate mixture. In one embodiment, the inorganic material is a highly porous xcex2-TCP material with a pore volume of at least 70% and interconnected micro-, meso-, and macro- porosity; and the biological material is bone marrow aspirate.
In a further embodiment of the present invention, there is provided a kit for the preparation and delivery of biologically active composites comprising an instrument for the injection and the withdrawal of one or more biological fluids and a porous, biocompatible material wherein the porous, biocompatible material comprises interconnected micro-, meso- and macro-porosity.